Reproductive and developmental risks from ethylene oxide: A probabilistic characterization of possible regulatory thresholds

Ethylene oxide is a gas produced in large quantities in the United States t hat is used primarily as a chemical intermediate in the production of ethyl ene glycol, propylene glycol, nonionic surfactants, ethanolamines, glycol e thers, and other chemicals. It has been well established that ethylene oxid e can induce cancer, genetic, reproductive and developmental, and acute hea lth effects in animals. The U.S. Environmental Protection Agency is current ly developing both a cancer potency factor and a reference concentration (R fC) for ethylene oxide. This study used the rich database on the reproducti ve and developmental effects of ethylene oxide to develop a probabilistic c haracterization of possible regulatory thresholds for ethylene oxide. This analysis was based on the standard regulatory approach for noncancer risk a ssessment, but involved several innovative elements, such as: (1) the use o f advanced statistical methods to account for correlations in developmental outcomes among littermates and allow for simultaneous control of covariate s (Such as litter size); (2) the application of a probabilistic approach fo r characterizing the uncertainty in extrapolating the animal results to hum ans; and (3) the use of a quantitative approach to account for the variatio n in heterogeneity among the human population. This article presents severa l classes of results, including: (1) probabilistic characterizations of ED( 10)s for two quantal reproductive outcomes-resorption and fetal death, (2) probabilistic characterizations of one developmental outcome-the dose expec ted to yield a 5% reduction in fetal (or pup) weight, (3) estimates of the RfCs that would result from using these values in the standard regulatory a pproach for noncancer risk assessment, and (4) a probabilistic characteriza tion of the level of ethylene oxide exposure that would be expected to yiel d a 1/1000 increase in the risk of reproductive or developmental outcomes i n exposed human populations.